High-dose interleukin-2 (IL-2) was the first immunotherapy approach to produce durable remissions in patients with advanced disease. However, these benefits were limited to a small fraction of patients, and treatment was associated with substantial toxicity.

The use of high-dose IL-2 in melanoma has largely been replaced by immunotherapy with checkpoint inhibitors directed against programmed death-1 protein (PD-1) alone or in combination with antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4). In addition, targeted therapy directed against the mitogen-activated protein (MAP) kinase pathway has provided an additional important treatment option for patients with advanced disease and a V600 mutation of BRAF.

The results with high-dose IL-2 and the potential role of other experimental immunotherapy approaches are reviewed here.

The principles of cancer immunotherapy and an overview of the treatment of metastatic melanoma are presented separately:

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